Thymol inhibits passive cutaneous anaphylaxis in mice through induction of apoptotic cell death in mast cells (177.3)

Abstract

Abstract Mast cells play a critical role in atopic dermatitis through the release of preformed and de novo synthesized pro-inflammatory mediators. In 1878, HR Crocker described the use of topical thymol in the treatment of advanced eczema. We hypothesized that the efficacy of thymol in eczema is due to a direct effect on mast cells. The effect of topical thymol was assessed on allergic murine ear swelling in the mast cell-dependent passive cutaneous anaphylaxis (PCA) model as well as on ear swelling directly and mast cells in vitro. Thymol dose-dependently inhibited PCA when administered topically prior to antigen challenge. Thymol induced a dose-dependent immediate ear swelling in mice, however lacked late phase swelling seen in PCA. This effect was associated with increased mast cell degranulation histologically and was inhibited in histamine deficient mice. Thymol induced mast cell degranulation and mRNA transcription in vitro, but prevented protein secretion. This was due to decreased mast cell viability from apoptosis. Mast cell activation from thymol occurred via sustained calcium flux. Thymol-induced calcium flux was not inhibited in TRPV3 KO mast cells, but was inhibited by HC-030031, a selective TRPA1 antagonist, and 2-APB, an IP3 receptor antagonist. However, HC-030031 and 2-APB were unable to prevent thymol-induced cell death. We are currently investigating the mechanism by which thymol leads to activation-induced cell death in mast cells.